HLA associations with leukemia

Frequencies of 35 HLA A, B, C, and DR antigens were determined in 1,834 leukemic Caucasoids to evaluate possible associations between HLA and leukemia. In comparison with the frequencies of HLA antigens in published controls, the frequency of Cw3 was significantly higher in patients with acute lymphoblastic leukemia (relative risk = 2.64, P less than 0.0002), acute myelogenous leukemia (relative risk = 1.92, P less than 0.0007), and chronic myelogenous leukemia (relative risk = 2.07, P less than 0.002; P values adjusted for multiple comparisons). The frequency of Cw4 was elevated in patients with acute lymphoblastic leukemia (relative risk = 2.01, P less than 0.0003), acute myelogenous leukemia (relative risk = 2.06, P less than 0.0002), and chronic myelogenous leukemia (relative risk = 2.14, P less than 0.0008). The frequency of Aw19 was significantly decreased in patients with acute myelogenous leukemia (relative risk = 0.68, P less than 0.01) and chronic myelogenous leukemia (relative risk = 0.59, P less than 0.005). None of the other 32 HLA antigens investigated had a statistically significant association with leukemia. The data suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes, while Aw19 may be a marker for decreased susceptibility to leukemia.     

Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung

Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.     

Unexplained hepatitis C virus antibody seroconversion in established blood donors

BACKGROUND: Understanding of the epidemiology and natural history of hepatitis C virus (HCV) infection is incomplete without reference to the early phase of infection. The prevalence of HCV infection is well documented in numerous reports. The seroconversion pattern in previously antibody-negative blood donors provides a model for the study of the incidence and transmission of HCV infection. STUDY DESIGN AND METHODS: Records of HCV antibody tests at the West Midlands Blood Transfusion Centre were reviewed to determine the seroconversion rate in 1994 among previously anti-HCV-negative blood donors. Seroconverting donors were counseled to investigate the possible routes of infection. RESULTS: In 1994, blood donations (n = 256,935) were collected from 149,370 donors; 24 donors (0.016%; 1/6224) were positive in the screening enzyme-linked immunosorbent assay (ELISA) and the third- generation recombinant immunoblot assay (RIBA-3). Two donors previously negative for HCV antibody in ELISA were positive in both tests in 1994. Four donors positive in ELISA and indeterminate in RIBA-3 in 1993 reacted positively in both tests in 1994. One donor negative for HCV antibody on previous screening reacted positively in ELISA and was indeterminate in RIBA-3 in 1994 and has become positive in both tests in 1995. A further 43 donors negative for HCV antibody on previous screening reacted positively in ELISA and were indeterminate in RIBA-3 in 1994. CONCLUSION: Documented seroconversion can take place in the absence of exposure to recognizable risk factors for the infection. The index donation or the donation immediately preceding seroconversion may be positive for HCV RNA in the polymerase chain reaction.     

Cluster headache pathogenesis: A pupillometric study

Thirty-two cluster headache patients and healthy controls (n = 16-20 for the various tests) were examined by means of a Whitaker pupillometer during pain-free intervals. Eye drops of the sympathomimetic agents tyramine, hydroxyamphetamine, and phenylephrine were instilled into the conjunctival sacs on separate occasions, and pupillary diameters recorded at standard time intervals. The mydriatic responses of the two pupils were compared. A moderate, but statistically significant, basal relative miosis was found on the pain side in cluster headache. The symptomatic-side pupils were less responsive than their counterparts when stimulated with tyramine and hydroxyamphetamine, the difference being statistically significant for the OH-amphetamine test. With the phenylephrine test, however, the mydriasis on the symptomatic side significantly exceeded that of the contralateral pupil. This pattern of reactions does not quite correspond to those of "ordinary" Horner's syndrome (1st, 2nd, and 3rd neuron lesion). There are, however, gross similarities with the recently reported pattern in central sympathetic neuron dysfunction. In cluster headache there is probably a "Horner-like picture" rather than a proper Horner's syndrome.